JP2014510152A5 - - Google Patents

Claims (37)

A method of reducing the viscosity of a formulation comprising acetate and therapeutic protein , comprising: (a) providing a formulation comprising acetate; and (b) adding glycine and / or arginine to the formulation. The viscosity of a formulation comprising glycine and / or arginine is compared to the viscosity of the same formulation without glycine and / or arginine, comprising adding to a concentration of 1.0% w / v Reduced, the way.   The viscosity of the formulation comprising glycine and / or arginine is at least about 5%, at least about 10%, at least about 15%, at least about 20 compared to the viscosity of the formulation in the absence of glycine and / or arginine. The method of claim 1, wherein the method is reduced by%, at least about 25%, or at least about 30%.   3. The method of claim 1 or 2, wherein the formulation comprising glycine and / or arginine has a viscosity of less than about 25 cP or less than about 20 cP. A method for reducing the viscosity of a formulation comprising acetate and therapeutic protein , comprising: (a) providing a formulation comprising acetate; and (b) about 0.04% methionine in the formulation. a method comprising adding to a concentration of w / v, wherein the viscosity of the formulation containing methionine is reduced compared to the viscosity of the same formulation without methionine.   The viscosity of the formulation comprising methionine is at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, or the viscosity of the formulation in the absence of methionine, or 5. The method of claim 4, wherein the method is reduced by at least about 30%.   6. The method of claim 4 or 5, wherein the formulation comprising methionine has a viscosity of less than about 25 cP or less than about 20 cP. A method for reducing the viscosity of a formulation comprising acetate and therapeutic protein , comprising: (a) providing a formulation comprising acetate; and (b) about 0.8% phenylalanine in the formulation. a method comprising adding to a concentration of w / v, wherein the viscosity of a formulation comprising phenylalanine is reduced relative to the viscosity of the same formulation without phenylalanine.   The viscosity of the formulation comprising phenylalanine is at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least compared to the viscosity of the formulation in the absence of phenylalanine 8. The method of claim 7, wherein the method is reduced by about 30%, at least about 40%, or at least about 50%.   9. The method of claim 7 or 8, wherein the formulation comprising phenylalanine has a viscosity of less than about 20 cP or less than about 15 cP. A method for reducing the viscosity of a formulation comprising acetate and therapeutic protein , comprising: (a) providing a formulation comprising acetate; and (b) about 0.2% tryptophan in the formulation. a method comprising adding to a concentration of w / v, wherein the viscosity of a formulation comprising tryptophan is reduced relative to the viscosity of the same formulation without tryptophan.   The viscosity of the formulation comprising tryptophan is at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least compared to the viscosity of the formulation in the absence of tryptophan 12. The method of claim 10, wherein the method is reduced by about 30%, at least about 40%, or at least about 50%.   12. The method of claim 10 or 11, wherein the viscosity of the formulation comprising tryptophan is less than about 20 cP or less than about 15 cP. A method for reducing the viscosity of a formulation comprising acetate and therapeutic protein , comprising: (a) providing a formulation comprising acetate; and (b) about 4.0% proline in the formulation. a method comprising adding to a concentration of w / v, wherein the viscosity of the formulation containing proline is reduced compared to the viscosity of the same formulation without proline.   The viscosity of the formulation comprising proline is at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, or compared to the viscosity of the formulation in the absence of proline, or 14. The method of claim 13, wherein the method is reduced by at least about 30%.   15. The method of claim 13 or 14, wherein the formulation comprising proline has a viscosity of less than about 25 cP or less than about 20 cP.   16. The method of any one of claims 1-15, further comprising determining the stability of the protein formulation.   17. A method according to any one of claims 1 to 16, wherein the formulation further comprises sucrose.   The method of claim 17, wherein the formulation further comprises sucrose at a concentration of about 234 mM.   19. A method according to any one of the preceding claims, wherein the formulation is formulated at a pH of about 5.5.   20. A method according to any one of the preceding claims, wherein the formulation further comprises polysorbate-80.   21. The method according to any one of claims 1 to 20, wherein the therapeutic protein is an antigen binding polypeptide.   The method according to any one of claims 1 to 21, wherein the antigen-binding polypeptide is an antibody.   23. The method of any one of claims 1-22, wherein the antigen binding polypeptide is an immunoglobulin single variable domain.   24. The method of claim 21, wherein the antigen binding polypeptide binds to interleukin 5 (IL5).   25. The method of claim 24, wherein the antigen binding polypeptide is an anti-IL5 antibody.   26. The method of claim 25, wherein the anti-IL5 antibody comprises a heavy chain comprising SEQ ID NO: 1 and a light chain comprising SEQ ID NO: 2.   The therapeutic protein is at a concentration of at least about 150 mg / ml, at least about 175 mg / ml, at least about 200 mg / ml, at least about 225 mg / ml, at least about 250 mg / ml, at least about 275 mg / ml, or at least about 300 mg / ml. 27. A method according to any one of claims 1 to 26, which is present.   28. The method of any one of claims 1-27, wherein the therapeutic protein is present at a concentration of at least about 150 mg / ml to about 300 mg / ml.   29. A method according to any one of claims 1 to 28, wherein the formulation is a reconstituted formulation.   30. The method of any one of claims 1-29, wherein the formulation is a liquid pharmaceutical formulation.   31. A method according to any one of claims 1-30, wherein the formulation is suitable for parenteral administration.   32. The method of any one of claims 1-31, wherein the formulation comprises from about 25 mM to about 75 mM acetate.   35. The method of claim 32, wherein the formulation comprises about 55 mM acetate. 34. A method of making a formulation comprising a reduced viscosity acetate salt and a therapeutic protein, the method comprising reducing the viscosity of the formulation according to the method of any one of claims 1-33. Method.   35. A stable formulation produced by the method of any one of claims 1-33 or the production method of claim 34.   36. A product comprising a container containing the formulation of claim 35.   40. The product of claim 36, further comprising instructions for administration of the formulation.